Gastrodin improves preeclampsia-induced cell apoptosis by regulation of TLR4/NF-κB in rats.

To explain gastrodin improved cell apoptosis induced by preeclampsia in vivo and in vitro study. The PE and normal rats were injected with normal saline (Model), low-dose gastrodin (Gas-L), medium-dose gastrodin (Gas-M), and high-dose gastrodin (Gas-H) groups at 50, 100, or 200 mg/kg per day. The rat blood pressure and 24-hr urine protein level were measured at pregnant days 10, 16, and 20. Evaluating pathology by H&E staining, the cell apoptosis by TUNEL, and MyD88 and NF-κB (p65) proteins by IHC assay using H/R to simulate PE cell model. Measuring cell proliferation, apoptosis, and MyD88 and NF-κB (p65) protein expression by MTT, flow cytometry, and WB assay. The SBP, DBP, and 24-hr urine protein levels were significantly different in PE rats (p < .05). The SBP, DBP, and 24-hr urine protein levels were significantly improved (p < .05) in vivo and in vitro. The positive apoptosis cells and apoptosis rate were significantly increased with MyD88 and NF-κB (p65) proteins upregulation (p < .05). The positive apoptosis cells and apoptosis rate were significantly decreased with MyD88 and NF-κB (p65) proteins depressing in gastrodin-treated groups with dose-dependent (p < .05). Gastrodin improves PE-induced cell apoptosis and pathology changed via MyD88/NF-κB pathway in vitro and in vivo study.

Histone deacetylase 6 negatively regulated microRNA-199a-5p induces the occurrence of preeclampsia by targeting VEGFA in vitro.

BACKGROUND: Preeclampsia (PE) is a special complication during pregnancy, which can cause severe maternal complications and lead the cause of maternal and perinatal death. So far, the etiology and pathogenesis of the disease is still not very clear. Currently, microRNAs (miRNAs) are reported to be the key regulators in the development of PE. METHODS: The miR-199a-5p expression was detected by qRT-PCR. The expression of vascular endothelial growth factor A (VEGFA), placental growth factor (PLGF) and activating transcription factor 3 (ATF-3) were detected by qRT-PCR and Western blot. Transwell-invasion assay wasused to assess the effects of miR-199a-5p, PLGF and ATF-3 on the invasion of HTR-8/SVneo and TEV-1cell lines. Western blot and qRT-PCR were used to assess the related molecular mechanisms. Dual luciferase reporter assay was used to detect the interaction between miR-199a-5p and VEGFA. RESULTS: Here, weinitially demonstrated that in PE tissues, miR-199a-5p expression was higher than that in normal tissues, while there was sharp reduction in VEGFA. In placental tissues of PE patients, miR-199a-5p exhibited a negatively correlation with VEGFA. The invasion of HTR-8/SVneo and TEV-1 cells was suppressed by miR-199a-5p through direct inhibition of VEGFA expression. In addition, PE tissues were associated with sharp reduction in the protein levels of PLGF, ATF-3 and histone deacetylase 6 (HDAC6) compared with the normal tissues. We further proved that over-expression of PLGF could also promote HTR-8/SVneo and TEV-1 cells invasion through up-regulating ATF-3 expression and down-regulating DNM3 opposite strand (DNM3os) and miR-199a-5p expression. Lastly, we also found that tubacin suppressed HTR-8/SVneo and TEV-1 cells invasion via regulation of miR-199a-5p and VEGFA expression. CONCLUSION: Our data demonstrated the role of miR-199a-5p in the preeclampsia, and proved that miR-199a-5p could act as a potential therapeutic target for the treatment of PE.